The p53 tumor suppressor potently limits the growth of immature and mature neurons under conditions of cellular stress. Although loss of p53 function contributes to the pathogenesis of central nervous system (CNS) tumors, excessive p53 function is implicated in neural tube defects, embryonic lethality, and neuronal degeneration. Thus, p53 function must be tightly controlled. The anti-proliferative properties of p53 are mediated, in part, through the induction of apoptosis, cell cycle arrest, and senescence. Although there is still much to be learned about the role of p53 in these processes, recent evidence supports exciting new roles for p53 in a wide range of processes, including neural precursor cell self-renewal, differentiation, and cell fate decisions. Understanding the full repertoire of p53 function in CNS development and tumorigenesis may provide us with novel points of therapeutic intervention for human diseases of the CNS.

Lyar/p53 mutant mice represent a new digenic model of NTDs. Furthermore, these studies identify Lyar as a novel candidate gene for a role in human NTDs. These results provide new data to support the idea that loss of a p53-mediated developmental checkpoint may increase the risk of NTDs owing to some germline mutations.

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